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A parasite's guide to editing scrambled genes

9 November 1991

By DAVID KING and DAVID CONCAR

In the 1980s, molecular biology’s founding creed – that DNA encodes
RNA which encodes protein – suffered a series of hefty blows. One of the
heftiest came from a puzzling genetic phenomenon discovered in the flagellum
of Trypanosoma brucei, an insect-borne parasite that causes sleeping sickness
in humans. In 1986 it emerged that the parasite has an unorthodox talent:
the ability to edit the information stored in some of its genes. Today,
after five years of hectic research and the discovery of many more examples
of gene editing, molecular biologists are close to unravelling its complex
molecular origins.

Robert Benne and his colleagues at the University of Amsterdam in the
Netherlands stumbled upon the phenomenon while examining genes belonging
to the parasite’s mitochondrion. (Like all so-called ‘kinetoplastid’ protozoans,
T. brucei has a single, large mitochondrion at the base of its flagellum.)
One of these genes, coding for a protein fragment, called COII, of the enzyme
cytochrome oxidase, was odd. One of its hundreds of linked nucleotides was
missing, something which should have rendered its coded information meaningless.
Yet – and here was the mystery – the parasite produced flawless copies of
the COII protein.

The key to the puzzle lay in RNA. The parasite was cannily correcting
the information by adding the missing nucleotide – a uridine unit – but
only after the gene had been copied into RNA. The concept of RNA editing
was thus born, shattering the dogma that genetic information always flows
unaltered from DNA into proteins. Certain cells, it seemed, could tamper
with their genetic information, and even add to it, en route.